Head and neck squamous cell carcinoma (HNSCC) is a disease comprised of two distinct entities: human papillomavirus (HPV) positive and HPV negative. HPV− disease is attributable to tobacco and alcohol use, and its declining incidence in the US has been ascribed to the well-publicized health risks of these activities. In stark contrast, HPV+ disease is on the rise, particularly in younger patient populations [1]. While improved response to traditional chemotherapies and thus favorable long-term survival is observed in HPV+ patients, prognoses remain grim for patients with advanced and metastatic tumors [2]. Furthermore, major quality of life issues arise due to treatment-related tissue damage [3]. Therefore, there is a need in the art for novel therapeutic targets and biomarkers for both HNSCC subsets. The instant disclosure seeks to address one or more of these needs in the art.